The regulation of blood pressure is maintained by various complex feedback circuits. These control systems include the heart and vascular system, baro- and chemoreceptors, the peripheral vegetative nervous system and vegetative nuclei in the central nervous system, the kidney, and several hormone systems, including both endocrine and paracrine pathways. The vegetative nervous system controls short-term adjustments ("short feedback-loop"), which enable physical activity as the reflex action, the renin-angiotensine system is the prominent medium-term control system. Long-term blood pressure adjustment is mediated by the kidneys by controlling the circulating volume; various hormone systems, including atrial natriuretic hormone , aldosterone , antidiuretic hormone , and medullolipids are involved in this pathways. There is general consent that essential hypertension is a multifactorial disease caused by both genetic and environmental factors. The hereditary nature of essential hypertension in humans is well established, both from epidemiological surveys [1, 2, 3], and from family studies, including the analyses of twin models [4, 5, 6]. The influence of genetic variance on blood pressure has been repeatedly demonstrated also in animal models of hypertension [7, 8, 9]. Due to the complexity of the regulatory system involved in blood pressure control, several candidate genes have been postulated. There exists good evidence from linkage studies and association studies, that polymorphisms of the angiotensine converting enzyme gene and the angiotensinogen gene are related to essential hypertension [10, 11, 12].
The adrenergic system appears to be a second control system which might be
linked to the
etiology of essential hypertension. Recent studies of our group favoured the hypothesis that
vascular adrenoceptors play an important role in the etiology of
hypertension. In a precursor
state of essential hypertension, namely salt sensitivity (see section
ss), a reduced amount of vasodilatatory 
-adrenergic
receptors both on circulating lymphocytes and on cultured skin fibroblasts was
demonstrated[13, 14, 15, 16, 17, 18].
In addition, preliminary experiments revealed a reduced
-adrenoceptor density on cultured
skin fibroblasts of hypertensive subjects as compared to matched
normotensive controls.
The present master's thesis
was undertaken in order (a) to search for mutations of the 2ar gene,
and (b) characterize alleles of the human -adrenergic receptor
through sequencing of the structure gene cloned into
pUC-18 vectors. This study represents a necessary first step to
perform association studies and linkage studies in subjects with and without
hypertension.
Receptor: Receptor Codon, Codon Mutations